The total electric charge and time of application of galvanic currents to macrophages can optimize the release of IL-1β with low cell death.

Galvanic current has been emerging as a novel therapy to regenerate chronic tissue lesions, including musculoskeletal and dermatological lesions. Recently, the NLRP3 inflammasome and IL-1β release have been identified as a signaling pathway triggered upon galvanic current application. However, the parameters for the clinical application of galvanic current remain subjective to the experience of the facultative in charge.

Comparative evaluation of point of care assay with ELISA techniques for quantifying serum concentrations of ustekinumab in inflammatory bowel disease patients.

Objectives: To evaluate the analytical performance and clinical utility of the POC-AFIAS assay in comparison with two ELISA established assays for quantifying serum concentrations of ustekinumab.

Methods: A prospective study was conducted. Consecutive serum samples from adult patients undergoing treatment with ustekinumab were collected.

Pyroptosis leads to loss of centrosomal integrity in macrophages.

NLRP3 forms a multiprotein inflammasome complex to initiate the inflammatory response when macrophages sense infection or tissue damage, which leads to caspase-1 activation, maturation and release of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and Gasdermin-D (GSDMD) mediated pyroptosis. NLRP3 inflammasome activity must be controlled as unregulated and chronic inflammation underlies inflammatory and autoimmune diseases. Several findings uncovered that NLRP3 inflammasome activity is under the regulation of centrosome localized proteins such as NEK7 and HDAC6, however, whether the centrosome composition or structure is altered during the inflammasome activation is not known.

Access to healthcare among transgender and non-binary youth in Sweden and Spain: A qualitative analysis and comparison.

Background: Transgender and non-binary (TGNB) people tend to report worse health than cis people, however, despite an increased need for care, they face several barriers when trying to access healthcare. These barriers might be exacerbated when young age intersects with a trans identity, and so there is a need for studies highlighting the experiences of TGNB youth.

Aims: To explore and compare how TGNB youth (15-26 years old) in Sweden and Spain experienced their access to healthcare, in order to shed light on the strengths and limitations of different kinds of healthcare systems and improve healthcare provision and policy development.

Cell-specific Extracellular Vesicles and Their miRNA Cargo Released Into the Organ Preservation Solution During Cold Ischemia Storage as Biomarkers for Liver Transplant Outcomes.

Background: Liver transplantation (LT) is crucial for end-stage liver disease patients, but organ shortages persist. Donation after circulatory death (DCD) aims to broaden the donor pool but presents challenges. Complications like acute rejection, hepatic artery thrombosis, and biliary issues still impact posttransplant prognosis.

Age and sex differences in pharmaceutical contamination in a keystone scavenger.

Pharmaceutical contaminants have a recognized negative impact on wildlife health. However, there are still many knowledge gaps on the factors influencing exposure and metabolic processing of compound mixtures as a function of season and individual characteristics such as age and sex. We evaluated age and sex differences in a set of seventeen compounds, including eleven antibiotics, five NSAIDs and caffeine, evaluated by HPLC-MS-TOF analysis in griffon vultures (Gyps fulvus) from central Spain.

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1β release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1β release, as well as a specific inflammatory cytokine signature.

(,)-Equol 7-β-D-glucuronide, but not other circulating isoflavone metabolites, modulates migration and tubulogenesis in human aortic endothelial cells targeting the VEGF pathway.

Current knowledge indicates that the consumption of isoflavone-rich foodstuffs can have a beneficial impact on cardiovascular health. To what extent these isoflavones act as the main actors of that benefit is less clear. Genistein (GEN), daidzein (DAZ), and the DAZ-derived microbial metabolite equol (Eq) exhibit antiangiogenic effects , but their low bloodstream concentrations make it difficult to rationalize the effects.

Polyphenols as NLRP3 inflammasome modulators in cardiometabolic diseases: a review of studies.

The nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs) are components of the innate immune system, important in coordinating the inflammatory response. Among them, NLRP3 can form inflammasomes, multiprotein complexes activating the inflammatory caspase-1 and leading, through a cell death-mediated signaling cascade, to the release of several proinflammatory cytokines. Dietary polyphenols, plant secondary metabolites, have been reported to exhibit anti-inflammatory properties, although studies have focused most on their effect on the expression of the final circulating cytokines rather than on the upstream signals activating the NLRP3 inflammasome.

Endothelial cell activation mediated by cold ischemia-released mitochondria is partially inhibited by defibrotide and impacts on early allograft function following liver transplantation.

DAMPs (danger-associated molecular patterns) are self-molecules of the organism that appear after damage. The endothelium plays several roles in organ rejection, such as presenting alloantigens to T cells and contributing to the development of inflammation and thrombosis. This study aimed to assess whether DAMPs present in the organ preservation solution (OPS) after cold ischemic storage (CIS) contribute to exacerbating the endothelial response to an inflammatory challenge and whether defibrotide treatment could counteract this effect.

Comparative effectiveness and drug survival of biosimilar infliximab CPT-13 vs. reference infliximab in inflammatory bowel disease: A retrospective cohort study.

Background: Studies have investigated the efficacy and safety of switching to the biosimilar infliximab (CT-P13) in patients with inflammatory bowel disease (IBD). However, there is limited research directly comparing the effectiveness, drug survival, and pharmacokinetic profiles of the reference infliximab (IFX) and CT-P13 in real clinical settings.

Objective: To compare the effectiveness and drug survival of CPT-13 and reference IFX at weeks 26 and 52, and to determine the pharmacokinetic profiles and safety profile in real-world settings.

Age and Sex Determine Electrocardiogram Parameters in the .

Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important risk factor. Preclinical models provide supportive evidence toward age-related cardiac changes, as well as allow for the study of pathological aspects of the disease. In the present work, we evaluated the electrocardiogram (ECG) recording in the during the aging process in both females and males.

7-Nitroindazole reduces L-DOPA-induced dyskinesias in non-human Parkinsonian primate.

Nitric oxide (NO) plays a pivotal role in integrating dopamine transmission in the basal ganglia and has been implicated in the pathogenesis of Parkinson disease (PD). The objective of this study was to ascertain whether the NO synthase inhibitor, 7-nitroindazole (7-NI), is able to reduce L-DOPA-induced dyskinesias (LIDs) in a non-human primate model of PD chronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Six Parkinsonian macaques were treated daily with L-DOPA for 3-4 months until they developed LIDs.

Recommendations for the future management of thrombocytopenia in patients with liver cirrhosis: A modified RAND/UCLA appropriateness method.

Objective: The lack of consensus and specific guidelines, and the introduction of new treatments in thrombocytopenia management in liver cirrhosis patients, required a series of recommendations by experts to improve knowledge on this disease. This study's aim was to improve the knowledge around thrombocytopenia in liver cirrhosis patients, in order to contribute to the generation of future evidence to improve the management of this disease.

Patients And Methods: A modified version of the RAND/UCLA appropriateness method was used.

Molecular identity of the lateral lemniscus nuclei in the adult mouse brain.

The dorsal (DLL), intermediate (ILL), and ventral (VLL) lateral lemniscus nuclei are relay centers in the central auditory pathway of the brainstem, commonly referred to as the lateral lemniscus nuclei (LLN). The LLN are situated in the prepontine and pontine hindbrain, from rhombomeres 1 to 4, extending from the more rostral DLL to the caudal VLL, with the ILL lying in between. These nuclei can be distinguished morphologically and by topological and connectivity criteria, and here, we set out to further characterize the molecular nature of each LLN.

Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantation.

Background: Innate immunity plays a fundamental role in solid organ transplantation. Myeloid cells can sense danger signals or DAMPs released after tissue or cell damage, such as during ischemia processes. This study aimed to identify DAMPs released during cold ischemia storage of human liver and analyze their ability to activate the inflammasome in myeloid cells and the possible implications in terms of short-term outcomes of liver transplantation.

Emerging Role of NLRP3 Inflammasome and Pyroptosis in Liver Transplantation.

The nucleotide-binding domain leucine-rich repeat-receptor, pyrin domain-containing-3 (NLRP3) inflammasome contributes to the inflammatory response by activating caspase-1, which in turn participates in the maturation of interleukin (IL)-1β and IL-18, which are mainly secreted via pyroptosis. Pyroptosis is a lytic type of cell death that is controlled by caspase-1 processing gasdermin D. The amino-terminal fragment of gasdermin D inserts into the plasma membrane, creating stable pores and enabling the release of several proinflammatory factors.

P2X7 receptor activation impairs antitumour activity of natural killer cells.

Background And Purpose: A high number of intratumoural infiltrating natural killer (NK) cells is associated with better survival in several types of cancer, constituting an important first line of defence against tumours. Hypoxia in the core of solid tumours induces cellular stress and ATP release into the extracellular space where it triggers purinergic receptor activation on tumour-associated immune cells. The aim of this study was to assess whether activation of the purinergic receptor P2X7 by extracellular ATP plays a role in the NK cells antitumour activity.